EFRI DCheM: Distributed Manufacturing of Personalized Medicines

EFRI DCheM：个性化药品的分布式制造

• 批准号: 2029139
• 负责人: Max Shtein
• 金额: $ 200万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2029139&HistoricalAwards=false
• 关键词: EFRI; DCheM; Distributed; Manufacturing; Personalized

On a dollar per mass basis, active pharmaceutical ingredients (APIs) are perhaps the most valuable chemicals in the world, and yet much of the mass of APIs in drugs taken is not absorbed in the body, entering the water supply and potentially harming human health and the environment. At the same time, despite rapid advances in the science of personalized medicine, and digital, additive manufacturing, the trillion-dollar-per-year pharmaceutical industry retains its century-old manufacturing processes and uses supply chain and distribution models that are potentially prone to tampering, contamination, and disruption. To address this problem, researchers and drug manufacturers have begun developing 3D printing approaches, as well as techniques borrowed from other industries (e.g. thin-film coatings) for drug formulation, dose customization, and release profile engineering. However, fundamental challenges remain with material compatibilities, ingredient dispersion in solvents or matrix materials, process control, and scalability. This fundamental research project aims to address these challenges by converging several new breakthroughs in additive manufacturing, molecular and crystallization modeling, surface science and engineering, and patient-specific in vitro disease models. This project will train students of diverse backgrounds, including women and minorities, and those concerned with patient care and safety, public health, drug costs, regulatory law and practices.This fundamental research project will introduce a radically new approach to drug formulation and distributed manufacturing, offering new means of controlling crystalline structure, cocrystallization, and adaptation to different delivery vehicles. Currently, predictive model-based process design for organic crystallization processes is still in relative infancy. Likewise, processes for cocrystallization require further work to systematize coformer selection and prediction of conditions for cocrystal formation. The novel, solvent-free process used here offers possibilities for developing novel pharmaceutical cocrystallization research tools, as well as a path to scalable cocrystal manufacturing. The technology platform of controlled surface wettability patterns to enable low-cost dissolution assays, combined with the organoid assays will create new paradigms for on-site validation and control of product quality, which will be particularly beneficial in a distributed manufacturing setting. The organoid assays used could enable rapid testing of new medications in more realistic cellular microenvironments prior to human trials. This research will facilitate the path to accelerating the time from drug development to manufacturing and distribution, and help prevent potentially dangerous by-products or contaminants from reaching patients.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

以每质量1美元计算，活性药物成分(API)可能是世界上最有价值的化学品，但所服用药物中的大部分API质量并未被人体吸收，进入供水系统，并可能损害人类健康和环境。与此同时，尽管个性化医学和数字添加剂制造科学取得了快速进步，但每年数万亿美元的制药行业仍保留着其百年历史的制造工艺，并使用供应链和分销模式，这些模式可能容易受到篡改、污染和破坏。为了解决这个问题，研究人员和药品制造商已经开始开发3D打印方法，以及借鉴其他行业(如薄膜涂层)的技术，用于药物配方、剂量定制和释放曲线工程。然而，在材料兼容性、成分在溶剂或基质材料中的分散、工艺控制和可扩展性方面仍存在根本挑战。这一基础研究项目旨在通过汇聚添加剂制造、分子和结晶建模、表面科学和工程以及患者特定体外疾病模型方面的几项新突破来应对这些挑战。这个项目将培训不同背景的学生，包括妇女和少数族裔，以及与患者护理和安全、公共卫生、药品成本、监管法律和实践有关的学生。这个基础研究项目将引入一种全新的药物配方和分布式制造方法，提供控制晶体结构、共结晶和适应不同递送工具的新方法。目前，基于预测模型的有机结晶过程工艺设计还处于起步阶段。同样，共结晶过程需要进一步的工作，使共晶器的选择和共晶形成条件的预测系统化。这里使用的新的、无溶剂的工艺为开发新型药物共结晶研究工具提供了可能性，并为可扩展的共晶制造提供了一条途径。受控表面润湿性模式的技术平台能够实现低成本的溶解分析，与有机物分析相结合将为现场验证和控制产品质量创造新的范例，这在分布式制造环境中将特别有益。使用的有机物分析可以在人体试验之前，在更真实的细胞微环境中快速测试新药。这项研究将有助于加快从药物开发到制造和分销的时间，并有助于防止潜在危险的副产品或污染物到达患者手中。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Personalized models of heterogeneous 3D epithelial tumor microenvironments: Ovarian cancer as a model.

• DOI: 10.1016/j.actbio.2021.04.041
• 发表时间: 2021-09-15
• 期刊: Acta biomaterialia
• 影响因子: 9.7
• 作者: Horst EN;Bregenzer ME;Mehta P;Snyder CS;Repetto T;Yang-Hartwich Y;Mehta G
• 通讯作者: Mehta G

Injectable three-dimensional tumor microenvironments to study mechanobiology in ovarian cancer.

• DOI: 10.1016/j.actbio.2022.04.039
• 发表时间: 2022-07-01
• 期刊: ACTA BIOMATERIALIA
• 影响因子: 9.7
• 作者: Horst, Eric N.;Novak, Caymen M.;Burkhard, Kathleen;Snyder, Catherine S.;Verma, Rhea;Crochran, Darel E.;Geza, Izabella A.;Fermanich, Wesley;Mehta, Pooja;Schlautman, Denise C.;Tran, Linh A.;Brezenger, Michael E.;Mehta, Geeta
• 通讯作者: Mehta, Geeta

Gas-Assisted Cocrystal Desublimation

• DOI: 10.1021/acs.cgd.1c01241
• 发表时间: 2022-02
• 期刊: Crystal Growth & Design
• 影响因子: 3.8
• 作者: Shea Sanvordenker;Siddharth Borsadia;Steven A. Morris;N. Rodríguez-Hornedo;M. Shtein